The delivery of cellular and molecular therapies to the spinal cord holds significant promise for the treatment of traumatic, autoimmune, degenerative and functional spinal cord diseases, all of which are thought to result from compromised neuronal connectivity due to a combination of axonal disruption and cell body death. In an attempt to address pathogenic mechanisms underlying these conditions, therapeutic strategies have been proposed that promote neuroprotection, axonal regeneration, and/or cell-based neurorestoration through replacement of lost neural tissue or supporting stroma.
A variety of in vitro and small animal in vivo experiments demonstrate motor neuron protection and axonal regeneration through the delivery of genes for trophic factors (e.g., IGF-1, GDNF), antiapoptotic proteins (e.g., XIAP, Bcl-xL), or siRNA capable of inactivating toxic gene products (e.g., SOD1 siRNA). Vectors designed for the delivery of these genes can be injected directly into the spinal cord (in vivo gene transfer) or delivered to cells which are subsequently transplanted into the spinal cord (ex vivo gene transfer).
Some form of guidance is needed to improve localization of the therapy to the tract or neurons of interest and to reduce the incidence of off-target sequelae. Stabilization has the dual function of increasing targeting precision while also reducing sequelae as the spinal cord can remain cannulated for a period of several minutes during targeting and the infusion process. Recent successes in cell-based therapy experimentation and the proprietary development of viral vectors designed for direct parenchymal injection require a technology capable of targeted, localized administration of a biologic payload to the spinal cord.